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1.
Adv Exp Med Biol ; 1428: 31-70, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37466768

RESUMO

Accumulating evidence suggests that an altered maternal milieu and environmental insults during the intrauterine and perinatal periods of life affect the developing organism, leading to detrimental long-term outcomes and often to adult pathologies through programming effects. Hormones, together with growth factors, play critical roles in the regulation of maternal-fetal and maternal-neonate interfaces, and alterations in any of them may lead to programming effects on the developing organism. In this chapter, we will review the role of sex steroids, thyroid hormones, and insulin-like growth factors, as crucial factors involved in physiological processes during pregnancy and lactation, and their role in developmental programming effects during fetal and early neonatal life. Also, we will consider epidemiological evidence and data from animal models of altered maternal hormonal environments and focus on the role of different tissues in the establishment of maternal and fetus/infant interaction. Finally, we will identify unresolved questions and discuss potential future research directions.


Assuntos
Desenvolvimento Fetal , Hormônios Tireóideos , Gravidez , Animais , Feminino , Desenvolvimento Fetal/fisiologia , Feto
2.
J Am Chem Soc ; 144(45): 20847-20853, 2022 11 16.
Artigo em Inglês | MEDLINE | ID: mdl-36331927

RESUMO

Level anticrossings (LACs) are ubiquitous in quantum systems and have been exploited for spin-order transfer in hyperpolarized nuclear magnetic resonance spectroscopy. This paper examines the manifestations of adiabatic passage through a specific type of LAC found in homonuclear systems of chemically inequivalent coupled protons incorporating parahydrogen (pH2). Adiabatic passage through such a LAC is shown to elicit translation of the pH2 spin order. As an example, with prospective applications in biomedicine, proton spin polarizations of at least 19.8 ± 2.6% on the methylene protons and 68.7 ± 0.5% on the vinylic protons of selectively deuterated allyl pyruvate ester are demonstrated experimentally. After ultrasonic spray injection of a precursor solution containing propargyl pyruvate and a dissolved Rh catalyst into a chamber pressurized with 99% para-enriched H2, the products are collected and transported to a high magnetic field for NMR detection. The LAC-mediated hyperpolarization of the methylene protons is significant because of the stronger spin coupling to the pyruvate carbonyl 13C, setting up an ideal initial condition for subsequent coherence transfer by selective INEPT. Furthermore, the selective deuteration of the propargyl side arm increases the efficiency and polarization level. LAC-mediated translation of parahydrogen spin order completes the first step toward a new and highly efficient route for the 13C NMR signal enhancement of pyruvate via side-arm hydrogenation with parahydrogen.


Assuntos
Hidrogênio , Prótons , Hidrogênio/química , Espectroscopia de Ressonância Magnética , Imageamento por Ressonância Magnética/métodos , Ácido Pirúvico
3.
Chemphyschem ; 22(9): 822-827, 2021 05 05.
Artigo em Inglês | MEDLINE | ID: mdl-33689210

RESUMO

Side-arm hydrogenation (SAH) by homogeneous catalysis has extended the reach of the parahydrogen enhanced NMR technique to key metabolites such as pyruvate. However, homogeneous hydrogenation requires rapid separation of the dissolved catalyst and purification of the hyperpolarised species with a purity sufficient for safe in-vivo use. An alternate approach is to employ heterogeneous hydrogenation in a continuous-flow reactor, where separation from the solid catalysts is straightforward. Using a TiO2 -nanorod supported Rh catalyst, we demonstrate continuous-flow parahydrogen enhanced NMR by heterogeneous hydrogenation of a model SAH precursor, propargyl acetate, at a flow rate of 1.5 mL/min. Parahydrogen gas was introduced into the flowing solution phase using a novel tube-in-tube membrane dissolution device. Without much optimization, proton NMR signal enhancements of up to 297 (relative to the thermal equilibrium signals) at 9.4 Tesla were shown to be feasible on allyl-acetate at a continuous total yield of 33 %. The results are compared to those obtained with the standard batch-mode technique of parahydrogen bubbling through a suspension of the same catalyst.


Assuntos
Acetatos/química , Hidrogênio/química , Morfinanos/química , Catálise , Hidrogenação , Espectroscopia de Ressonância Magnética
4.
J Sex Marital Ther ; 46(1): 35-42, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31151369

RESUMO

This study evaluated whether attachment styles might be related to condomless sex, use of drugs, and adherence to antiretroviral treatment (ART) in 400 HIV-positive gay and bisexual men (GBM). With the Relationship Questionnaire, 160 men were classified as securely attached and 240 as insecurely attached (88 dismissive, 79 preoccupied, and 73 fearful). Insecurely attached GBM had more condomless sex (p = 0.04), and used more cocaine (p = 0.001), ecstasy (p = 0.03), GHB (p = 0.04), and ketamine (p = 0.04). No differences were observed in adherence to ART. Dismissively attached GBM reported more condomless sex and use of drugs than preoccupied and fearfully attached GBM. The perspective of attachment might enrich the interventions to promote heath care in GBM.


Assuntos
Bissexualidade/psicologia , Preservativos/estatística & dados numéricos , Medo/psicologia , Homossexualidade Masculina/psicologia , Apego ao Objeto , Parceiros Sexuais/psicologia , Adulto , Bissexualidade/estatística & dados numéricos , Mecanismos de Defesa , Homossexualidade Masculina/estatística & dados numéricos , Humanos , Masculino , Autoimagem , Adulto Jovem
5.
Stroke ; 50(2): 491-494, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30580706

RESUMO

Background and Purpose- The influence of age on the relationship between obstructive sleep apnea (OSA) and the incidence of hard cardiovascular events remains controversial. We sought to analyze the relationship between OSA and the incidence of stroke and coronary heart disease in a large cohort of elderly patients, as well as to investigate the role of continuous positive airway pressure (CPAP) treatment in these associations. Methods- Post hoc analysis of a prospective observational study of consecutive patients ≥65 years studied for OSA suspicion at 2 Spanish University Hospitals. Patients with an apnea-hypopnea index (AHI) <15 were the reference group. OSA was defined by an AHI ≥15 and classified as untreated (CPAP not prescribed or compliance <4 hours/day), mild-moderate (AHI 15-29), untreated severe (AHI ≥30), and CPAP-treated (AHI ≥15 and CPAP compliance ≥4 hours/day). Results- 859 and 794 elderly patients were included in the stroke and coronary heart disease analyses, respectively. The median (interquartile range) follow-up was 72 (50-88.5) and 71 (51.5-89) months, respectively. Compared with the reference group, the fully adjusted hazard ratios for the incidence of stroke were 3.42 (95% CI, 1.37-8.52), 1.02 (95% CI, 0.41-2.56), and 1.76 (95% CI, 0.62-4.97) for the untreated severe OSA group, CPAP-treated group, and untreated mild-moderate OSA group, respectively. No associations were shown between any of the different OSA groups and coronary heart disease incidence. Conclusions- The incidence of stroke, but not coronary heart disease, is increased in elderly patients with untreated severe OSA. Adequate CPAP treatment may reduce this risk.


Assuntos
Doença das Coronárias , Síndromes da Apneia do Sono , Acidente Vascular Cerebral , Idoso , Idoso de 80 Anos ou mais , Doença das Coronárias/epidemiologia , Doença das Coronárias/etiologia , Feminino , Humanos , Incidência , Masculino , Estudos Prospectivos , Índice de Gravidade de Doença , Síndromes da Apneia do Sono/complicações , Síndromes da Apneia do Sono/epidemiologia , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/etiologia
6.
AIDS Care ; 27(11): 1396-403, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26679268

RESUMO

Resilience is a predictor of emotional well-being and psychological adjustment in people living with HIV infection. We report the results of a cross-sectional study in which we evaluated resilience and its association with perception of ageing, coping strategies, quality of life, and emotional status in a group of long-term diagnosed HIV-infected patients. The analysis included 151 consecutive participants (57.6% men). Resilience was moderately high to high in 65 (43%) participants, moderately low to moderate in 57 (37.7%), and very low in 29 (19.2%). Univariate and multivariate analyses were performed. Two factors of perception of ageing (good cognitive self-concept and good subjective perception of social relationships), the use of positive reframing as a coping strategy and better emotional status remained associated with high resilience. Our findings suggest that successful ageing is possible in people living with HIV infection. Resilience seems to play a key role in the ageing process.


Assuntos
Adaptação Psicológica , Envelhecimento/psicologia , Infecções por HIV/psicologia , Qualidade de Vida/psicologia , Resiliência Psicológica , Estresse Psicológico/psicologia , Adulto , Idoso , Estudos Transversais , Feminino , Infecções por HIV/diagnóstico , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Percepção , Autoimagem , Ajustamento Social , Isolamento Social , Apoio Social , Fatores Socioeconômicos , Espanha , Estresse Psicológico/prevenção & controle
7.
AIDS Behav ; 18(4): 676-685, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24077971

RESUMO

Long-term diagnosed and treated HIV-infected patients have to cope with a wide range of challenges that threaten their ability to age successfully. We report the results of a randomized controlled trial testing the effects of a mindfulness-based cognitive therapy (MBCT) program on quality of life (QoL), emotional status, and immune status over a 3-month period. Forty HIV-infected patients diagnosed prior to 1996 and on cART for a minimum of 5 years were randomized to follow an MBCT program (n = 20) or remain as controls (routine follow-up) (n = 20). A regression analysis was performed, and the measurement of effect size was estimated using Cohen's d. QoL, psychological stress, depressive symptoms, and anxiety symptoms improved in the MBCT group compared with the control group. During follow-up, patients in the MBCT group had a significantly increased CD4 cell count. Effect sizes for MBCT on the variables assessed were large (d = 0.8). The findings suggest that this program may help to promote successful aging in these patients.

8.
Am J Respir Crit Care Med ; 187(8): 823-31, 2013 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-23392438

RESUMO

RATIONALE: The prevalence of bronchiectasis is high in patients with moderate-to-severe chronic obstructive pulmonary disease (COPD) and it has been associated with exacerbations and bacterial colonization. These have demonstrated some degree of prognostic value in patients with COPD but no information about the relationship between bronchiectasis and mortality in patients with COPD is currently available. OBJECTIVES: To assess the prognostic value of bronchiectasis in patients with moderate-to-severe COPD. METHODS: Multicenter prospective observational study in consecutive patients with moderate-to-severe COPD. Bronchiectasis was diagnosed by high-resolution computed tomography scan. A complete standardized protocol was used in all patients covering general, anthrophometric, functional, clinical, and microbiologic data. After follow-up, the vital status was recorded in all patients. Multivariate Cox analysis was used to determine the independent adjusted prognostic value of bronchiectasis. MEASUREMENTS AND MAIN RESULTS: Ninety-nine patients in Global Initiative for Chronic Obstructive Lung Disease (GOLD) II, 85 in GOLD III, and 17 in GOLD IV stages were included. Bronchiectasis was present in 115 (57.2%) patients. During the follow-up (median, 48 mo [interquartile range, 35-53]) there were 51 deaths (43 deaths in the bronchiectasic group). Bronchiectasis was associated with an increased risk of fully adjusted mortality (hazard ratio, 2.54; 95% confidence interval, 1.16-5.56; P = 0.02). CONCLUSIONS: Bronchiectasis was associated with an independent increased risk of all-cause mortality in patients with moderate-to-severe COPD.


Assuntos
Bronquiectasia/etiologia , Doença Pulmonar Obstrutiva Crônica/complicações , Idoso , Instituições de Assistência Ambulatorial/estatística & dados numéricos , Bronquiectasia/diagnóstico por imagem , Bronquiectasia/epidemiologia , Comorbidade , Progressão da Doença , Feminino , Humanos , Incidência , Estimativa de Kaplan-Meier , Masculino , Prevalência , Prognóstico , Modelos de Riscos Proporcionais , Estudos Prospectivos , Doença Pulmonar Obstrutiva Crônica/mortalidade , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Índice de Gravidade de Doença , Espanha/epidemiologia , Escarro/microbiologia , Tomografia Computadorizada por Raios X
9.
Clin Med Insights Endocrinol Diabetes ; 16: 11795514231196461, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37705939

RESUMO

Background: It is still unelucidated how hormonal alterations affect developing organisms and their descendants. Particularly, the effects of androgen levels are of clinical relevance as they are usually high in women with Polycystic Ovary Syndrome (PCOS). Moreover, it is still unknown how androgens may affect males' health and their descendants. Objectives: We aimed to evaluate the multigenerational effect of prenatal androgen excess until a second generation at early developmental stages considering both maternal and paternal effects. Design And Methods: This is an animal model study. Female rats (F0) were exposed to androgens during pregnancy by injections of 1 mg of testosterone to obtain prenatally hyperandrogenized (PH) animals (F1), leading to a well-known animal model that resembles PCOS features. A control (C) group was obtained by vehicle injections. The PH-F1 animals were crossed with C males (m) or females (f) and C animals were also mated, thus obtaining 3 different mating groups: Cf × Cm, PHf × Cm, Cf × PHm and their offspring (F2). Results: F1-PHf presented altered glucose metabolism and lipid profile compared to F1-C females. In addition, F1-PHf showed an increased time to mating with control males compared to the C group. At gestational day 14, we found alterations in glucose and total cholesterol serum levels and in the placental size of the pregnant F1-PHf and Cf mated to F1-PHm. The F2 offspring resulting from F1-PH mothers or fathers showed alterations in their growth, size, and glucose metabolism up to early post-natal development in a sex-dependent manner, being the females born to F1-PHf the most affected ones. Conclusion: androgen exposure during intrauterine life leads to programing effects in females and males that affect offspring health in a sex-dependent manner, at least up-to a second generation. In addition, this study suggests paternally mediated effects on the F2 offspring development.

10.
Front Psychiatry ; 14: 1055012, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36950257

RESUMO

Introduction: This systematic review aimed to answer whether we can predict subsequent social functioning in first episode psychosis (FEP) by means of an initial cognitive examination. In order to do this, we gathered longitudinal studies which evaluated neurocognition and/or social cognition regarding their impact on long-term social functioning of FEP patients. Methods: The MOOSE method was employed and 28 studies covering data from a total of 2572 patients with longitudinal trajectories from 2 months to 5 years were reviewed. Results: In general, cognitive deficits impacted on the social functioning of the FEP patients across the time. The neurocognitive domains which most closely predicted social functioning were processing speed, sustained attention and working memory. An overall cognitive dysfunction, low IQ and the academic trajectory were also found predictive. Regarding social cognition, the findings were not unanimous. Discussion: In addition of the impact of each variable, several of the articles found a complex relationship between social cognition, neurocognition, social functioning and negative symptoms, pointing social cognition as a modulator of neurocognition but being modulated as well by negative symptoms. The principal clinical implication of this review is that the initial assessment of FEP patients and their rehabilitation must take cognition into account.

11.
Theriogenology ; 198: 131-140, 2023 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-36584634

RESUMO

Prenatal androgen exposure induces fetal programming leading to alterations in offspring health and phenotypes that resemble those seen in women with Polycystic Ovary Syndrome. It has been described that prenatal androgenization affects the reproductive axis and leads to metabolic and endocrine disorders. Adipose tissue plays a crucial role in all these functions and is susceptible to programming effects. Particularly, gonadal adipose tissue is involved in reproductive functions, so dysfunctions in this tissue could be related to fertility alterations. We aimed to investigate the extent to which prenatal hyperandrogenization is able to alter the functionality of gonadal adipose tissue in female adult rats, including lipid metabolism, adipokines expression, and de novo synthesis of steroids. Pregnant rats were treated with 1 mg of testosterone from day 16 to day 19 of pregnancy, and female offspring were followed until 90 days of age, when they were euthanized. The prenatally hyperandrogenized (PH) female offspring displayed two phenotypes: irregular ovulatory (PHiov) and anovulatory (PHanov). Regarding lipid metabolism, both PH groups displayed disruptions in the main lipid pathways with altered levels of triglyceride and increased lipid peroxidation levels. In addition, we found that Peroxisome Proliferator-Activated Receptors (PPARs) alpha protein expression was decreased in both PH phenotypes (p < 0.05), but no changes were found in PPARγ protein levels. Furthermore, regarding adipokines, no changes were found in Leptin and Adiponectin protein levels, but Chemerin protein levels were decreased in the PHiov group (p < 0.05). Regarding de novo synthesis of steroids, the PHanov group showed increased protein levels of Cyp17a1 and Cyp19, while the PHiov group only showed decreased protein levels of Cyp19 (p < 0.05). These results suggest that prenatal androgen exposure affects females' gonadal adipose tissue in adulthood, disturbing different lipid pathways, Chemerin expression, and de novo synthesis of steroids.


Assuntos
Síndrome do Ovário Policístico , Efeitos Tardios da Exposição Pré-Natal , Gravidez , Ratos , Feminino , Animais , Androgênios , Aromatase , Síndrome do Ovário Policístico/metabolismo , Síndrome do Ovário Policístico/veterinária , Esteroides , Adipocinas , Triglicerídeos , Tecido Adiposo , Efeitos Tardios da Exposição Pré-Natal/veterinária
12.
Brain Behav Immun ; 26(4): 568-72, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-22306454

RESUMO

This study explores the role of psychological stress in the circulating levels of interleukin-6 (IL-6) in a group of HIV-1 infected individuals on effective cART. We developed a cross-sectional study with 50 individuals with confirmed diagnosis of HIV-1 infection ≥1 and ≤8 years, on continuous cART for >1 and <8 years and with plasma viral load <50 copies/mL for at least 1 year. Clinical, behavioral and psychological variables were collected to control their possible indirect contribution in the relationship between psychological stress and IL-6. Pearson correlation and univariate/multivariate logistic regressions were performed. Eighty-eight percent of the subjects were male: median (IQR) age: 39.0 (32.7-42.2), years since HIV-1 infection: 3.4 (2.1-7.0), years on cART: 2.5 (1.6-5.7), CD4 cell count: 709.0 (573.5-881.0) cell/mm(3), plasma levels of IL-6: 7.0 (0-12.2) pg/ml. A strong correlation between IL-6 and psychological stress was found (r=.81). Psychological stress (coef: 0.49; SD: 0.05), anxiety/depression (0.37; 0.08) and unhealthy diet (2.94; 1.38) were associated with higher levels of IL-6. In the multivariate model psychological stress remained strongly associated with IL-6 (R(2): 59%). In conclusion, individuals with psychological stress presented high levels of IL-6 and psychological stress was the only variable which remained strongly associated with IL-6. This strong relationship suggests evidence for a mechanism through which psychological stress might contribute to the health's impairment of HIV-infected individuals on effective cART.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Infecções por HIV , HIV-1 , Interleucina-6/imunologia , Estresse Psicológico/imunologia , Adulto , Ansiedade/imunologia , Ansiedade/psicologia , Estudos Transversais , Depressão/imunologia , Depressão/psicologia , Quimioterapia Combinada , Feminino , Infecções por HIV/tratamento farmacológico , Infecções por HIV/imunologia , Infecções por HIV/psicologia , Humanos , Interleucina-6/sangue , Masculino , Carga Viral
13.
WIREs Mech Dis ; 14(5): e1558, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35475329

RESUMO

Polycystic ovary syndrome (PCOS) is one of the major endocrine disorders affecting women of reproductive age. Its etiology remains unclear. It is suggested that environmental factors, and particularly the intrauterine environment, play key roles in PCOS development. Besides the role of androgens in PCOS pathogenesis, exposure to endocrine disruptors, as is Bisphenol A, could also contribute to its development. Although PCOS is considered one of the leading causes of ovarian infertility, many PCOS patients can get pregnant. Some of them by natural conception and others by assisted reproductive technique treatments. As hyperandrogenism (one of PCOS main features) affects ovarian and uterine functions, PCOS women, despite reaching pregnancy, could present high-risk pregnancies, including implantation failure, an increased risk of gestational diabetes, preeclampsia, and preterm birth. Moreover, hyperandrogenism may also be maintained in these women during pregnancy. Therefore, as an altered uterine milieu, including hormonal imbalance, could affect the developing organisms, monitoring these patients throughout pregnancy and their offspring development is highly relevant. The present review focuses on the impact of androgenism and PCOS on fertility issues and pregnancy-related outcomes and offspring development. The evidence suggests that the increased risk of pregnancy complications and adverse offspring outcomes of PCOS women would be due to the factors involved in the syndrome pathogenesis and the related co-morbidities. A better understanding of the involved mechanisms is still needed and could contribute to a better management of these women and their offspring. This article is categorized under: Reproductive System Diseases > Molecular and Cellular Physiology Reproductive System Diseases > Environmental Factors.


Assuntos
Hiperandrogenismo , Infertilidade , Síndrome do Ovário Policístico , Nascimento Prematuro , Feminino , Humanos , Hiperandrogenismo/complicações , Recém-Nascido , Infertilidade/complicações , Síndrome do Ovário Policístico/complicações , Gravidez , Resultado da Gravidez/epidemiologia , Nascimento Prematuro/etiologia
14.
J Dev Orig Health Dis ; 13(3): 300-309, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-34275515

RESUMO

It is known that prenatal hyperandrogenization induces alterations since early stages of life, contributing to the development of polycystic ovary syndrome affecting the reproductive axis and the metabolic status, thus promoting others associated disorders, such as dyslipidemia, insulin resistance, liver dysfunction, and even steatosis. In this study, we aimed to evaluate the effect of fetal programming by androgen excess on the hepatic lipid content and metabolic mediators at adult life. Pregnant rats were hyperandrogenized with daily subcutaneous injections of 1 mg of free testosterone from days 16 to 19 of pregnancy. The prenatally hyperandrogenized (PH) female offspring displayed two phenotypes: irregular ovulatory phenotype (PHiov) and anovulatory phenotype (PHanov), with different metabolic and endocrine features. We evaluated the liver lipid content and the main aspect of the balance between fatty acid (FA) synthesis and oxidation. We investigated the status of the peroxisomal proliferator-activated receptors (PPARs) alpha and gamma, which act as lipid mediators, and the adipokine chemerin, one marker of liver alterations. We found that prenatal hyperandrogenization altered the liver lipid profile with increased FAs levels in the PHanov phenotype and decreased cholesterol content in the PHiov phenotype. FA metabolism was also disturbed, including decreased mRNA and protein PPARgamma levels and impaired gene expression of the main enzymes involved in lipid metabolism. Moreover, we found low chemerin protein levels in both PH phenotypes. In conclusion, these data suggest that prenatal hyperandrogenization exerts a negative effect on the liver and alters lipid content and metabolic mediators' expression at adult age.


Assuntos
PPAR gama , Efeitos Tardios da Exposição Pré-Natal , Androgênios/metabolismo , Animais , Feminino , Desenvolvimento Fetal , Humanos , Metabolismo dos Lipídeos , Lipídeos , Fígado/metabolismo , PPAR gama/metabolismo , PPAR gama/farmacologia , Gravidez , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Ratos , Ratos Sprague-Dawley
15.
Curr Med Chem ; 28(27): 5625-5647, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33413060

RESUMO

BACKGROUND: Lipids are essential components of cells that participate in metabolic and endocrine regulation and reproductive functions. The main organs where lipid regulation takes place are the liver and adipose tissue. Besides, when each tissue- specific action cannot be exerted, it could lead to several endocrine-metabolic disorders closely related to PCOS, such as non-alcoholic fatty liver disease (NAFLD) and obesity. OBJECTIVE: This work aims to discuss the impact of lipid alterations on metabolic and reproductive health. Therefore, this review focus on the importance of carrying out an integrated study of the molecular pathways affected in PCOS for developing target therapies. RESULTS: Lipids play a major role in PCOS pathogenesis. In this regard, failures in lipid regulation, synthesis, and/or homeostasis contribute to metabolic and reproductive abnormalities, such as those seen in PCOS. Several lipid pathways and regulators are altered in this pathology, leading to dysfunctions that worsen reproductive functions. Therefore, there are several treatments to manage dyslipidemias. Non-pharmacological therapies are considered a first-line treatment being the pharmacological treatments a second-line option. CONCLUSION: The best treatment to improve the lipid profile is lifestyle intervention, a combination of hypocaloric diet and exercise. Regarding pharmacological therapies, a combination of fibrate and statins would be the most recommended drugs. Still, in PCOS women, treatment with metformin or TZDs not only modulates the lipid metabolism, but also improves ovulation. In addition, metformin with lifestyle interventions has positive effects on the metabolic and reproductive features of PCOS patients.


Assuntos
Resistência à Insulina , Metformina , Síndrome do Ovário Policístico , Dieta Redutora , Feminino , Humanos , Metabolismo dos Lipídeos , Obesidade/terapia , Síndrome do Ovário Policístico/terapia , Saúde Reprodutiva
16.
Mol Cell Endocrinol ; 519: 111045, 2021 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-33148513

RESUMO

Prenatal androgen excess is considered one of the main causes of the development of polycystic ovary syndrome. In this study, we investigated the effect of prenatal hyperandrogenization (PH) on the physiology of the adult uterine tissue using a murine model of fetal programming caused by androgen excess in adult female rats. Pregnant rats were hyperandrogenized with testosterone and female offspring were studied when adult. Our results showed that PH leads to hyperglycemia and hyperinsulinemia. Consequently, PH developed insulin resistance and a systemic inflammatory state reflected by increased C-reactive protein. In the uterine tissue, levels of PPAR gamma-an important metabolic sensor in the endometrium-were found to be impaired. Moreover, PH induced a pro-inflammatory and an unbalanced oxidative state in the uterus reflected by increased COX-2, lipid peroxidation, and NF-κB. In summary, our results revealed that PH leads to a compromised metabolic state likely consequence of fetal reprogramming.


Assuntos
Inflamação/patologia , Resistência à Insulina , Estresse Oxidativo , Efeitos Tardios da Exposição Pré-Natal/patologia , Testosterona/efeitos adversos , Útero/patologia , Androgênios/efeitos adversos , Animais , Antioxidantes/metabolismo , Biomarcadores/metabolismo , Ciclo-Oxigenase 2/metabolismo , Feminino , Glicogênio Sintase Quinase 3 beta/metabolismo , Tamanho do Órgão , Oxirredução , PPAR gama/metabolismo , Fosforilação , Gravidez , Ratos Sprague-Dawley , Útero/metabolismo
17.
J Magn Reson ; 321: 106869, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33197680

RESUMO

Nuclear spin hyperpolarization derived from parahydrogen can enable nuclear magnetic resonance spectroscopy and imaging with sensitivity enhancements exceeding four orders of magnitude. The NMR signal enhancement is proportional to 4xp-1, where xp is the parahydrogen mole fraction. For convenience, many labs elect to carry out the ortho-para conversion at 77 K where 50% enrichment is obtained. In theory, enrichment to 100% yields an automatic three-fold increase in the NMR signal enhancement. Herein, construction and testing of a simple and inexpensive continuous-flow converter for high para-enrichment is described. During operation, the converter is immersed in liquid helium contained in a transport dewar of the type commonly found in NMR labs for filling superconducting magnets. A maximum enrichment of 97.3±1.9% at 30 K was observed at 4.5 bar and 300 mL/min flow rate. The theoretically predicted 2.9-fold increase in the signal enhancement factor was confirmed in the heterogeneous hydrogenation of propene to propane over a PdIn/SBA-15 catalyst. The relatively low-cost to construct and operate this system could make high parahydrogen enrichment, and the associated increase in the parahydrogen-derived NMR signals, more widely accessible.

18.
J Endocrinol ; 247(3): 239-250, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33112815

RESUMO

Prenatal androgen exposure affects reproductive functions and has been proposed as an underlying cause of polycystic ovary syndrome (PCOS). In this study, we aimed to investigate the impact of prenatal androgen exposure on ovarian lipid metabolism and to deepen our understanding of steroidogenesis regulation during adulthood. Pregnant rats were hyperandrogenized with testosterone and female offspring were studied when adult. This treatment leads to two different phenotypes: irregular ovulatory and anovulatory animals. Our results showed that prenatally hyperandrogenized (PH) animals displayed altered lipid and hormonal profile together with alterations in steroidogenesis and ovarian lipid metabolism. Moreover, PH animals showed alterations in the PPARg system, impaired mRNA levels of cholesterol receptors (Ldlr and Srb1) and decreased expression of the rate-limiting enzyme of de novo cholesterol production (Hmgcr). Anovulatory PH animals presented an increase of ovarian cholesteryl esters levels and lipid peroxidation index. Together with alterations in cholesterol metabolism, we found an impairment of the steroidogenic pathway in PH animals in a phenotype-specific manner. Regarding fatty acid metabolism, our results showed, in PH animals, an altered expression of Srebp1 and Atgl, which are involved in fatty acid metabolism and triglycerides hydrolysis, respectively. In conclusion, fatty acid and cholesterol metabolism, which are key players in steroidogenesis acting as a source of energy and substrate for steroid production, were affected in animals exposed to androgens during gestation. These results suggest that prenatal androgen exposure leads to long-term effects that affect ovary lipid metabolism and ovarian steroid formation from the very first steps.


Assuntos
Hormônios Esteroides Gonadais/biossíntese , Metabolismo dos Lipídeos/fisiologia , Ovário/metabolismo , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Testosterona/administração & dosagem , Animais , Colesterol/metabolismo , Feminino , Metabolismo dos Lipídeos/efeitos dos fármacos , Ovário/efeitos dos fármacos , Gravidez , Ratos
19.
Nanoscale ; 12(15): 8519-8524, 2020 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-32242595

RESUMO

The molecular basis for the high cis-alkene selectivity over intermetallic PtSn for alkyne semi-hydrogenation is demonstrated. Unlike the universal assumption that the bimetallic surface is saturated with atomic hydrogen, molecular hydrogen has a higher barrier for dissociative adsorption on intermetallic PtSn due to the deficiency of Pt three-fold sites. The resulting molecular behavior of adsorbed hydrogen on intermetallic PtSn nanoparticles leads to pairwise-hydrogenation of three alkynes to the corresponding cis-alkenes, satisfying both high stereoselectivity and high chemoselectivity.

20.
Methods Mol Biol ; 1955: 105-118, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30868522

RESUMO

Trypanosomatids are unicellular organisms that colonize a wide diversity of environments and hosts. For instance, Trypanosoma cruzi is a human pathogen responsible for Chagas diseases, while Leishmania tarentolae infects amphibians and became a biotechnological tool suitable for recombinant protein expression. T. cruzi antigens are needed for the development of improved epitope-based methods for diagnosis and treatment of Chagas disease. Molecular cloning for the production of recombinant proteins offers the possibility to obtain T. cruzi antigens at high yield and purity. L. tarentolae appears as the ideal expression host to obtain recombinant T. cruzi antigens with a structure and posttranslational modifications typical of trypanosomatids. In this chapter, we present a protocol for the analytical to mid-scale production of recombinant T. cruzi antigens, using L. tarentolae as expression host (LEXSY® inducible system).


Assuntos
Antígenos de Protozoários/genética , Clonagem Molecular/métodos , Leishmania/genética , Trypanosoma cruzi/genética , Doença de Chagas/parasitologia , Vetores Genéticos/genética , Humanos , Plasmídeos/genética , Proteínas Recombinantes/genética , Transfecção/métodos
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